We have developed a potential immunotherapeutic for deadly S. aureus infections that enhances neutrophil recruitment, and killing of this superbug by conjugating two elements together – a peptide chemoattractant, and a cell wall binding element. This strategy exploits formylated peptides as chemoattractants, which activate innate immune cells by binding to formylated peptide receptor, a G protein-coupled receptor (GPCR). With the peptide chemoattractant being linked to a cell wall binding element, S. aureus becomes decorated with the formylated peptide and the chemoattract gradient is enhanced around the site of infection. This gradient acts as a guiding light for neutrophils, first line responders of the innate immune system that are essential for a successful immune response to infection. This strategy ensures that S. aureus can no longer hide and evade our innate immune defences to establish infections – taking away the superbug’s superpower of invisibility. A superpower that often becomes stronger and more effective as the bacteria develop resistance to more antibiotics. It is therefore no surprise that S. aureus, with its superpowers of invisibility to our immune defences and invincibility to our treatment strategies, that Methicillin-resistant S. aureus (MRSA) strains alone cause 10,000 death a year in the USA. These antibiotic resistant strains are becoming all too common in hospital settings. We are therefore in desperate need of new strategies like our potential immunotherapeutic to combat superbug infections.
Using the combination of in vitro assays, and infection-on-a-chip, we have determined that this immunotherapeutic enhances the recruitment, engulfment, and killing of S. aureus by human neutrophils. In this process we have generated a library of formylated peptides, which established that the peptide sequence is important for this enhancement of neutrophil activity through the activation of a GPCR. This offers an immunotherapeutic kryptonite that deprives superbugs of their superpowers.